S0636: Erlotinib and Bevacizumab in Never-Smokers With Stage IIIB or Stage IV Primary Non-Small Cell Lung Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  • Adenocarcinoma

    • No component of squamous cell carcinoma present
  • Incompletely resected or unresectable disease

• Stage IIIB or IV disease as defined below:

  • Selected stage IIIB disease

    • T4 (cytologically confirmed malignant pleural effusion OR pleural tumor foci that are separate from direct pleural invasion by the primary tumor)
    • Any N
    • M0

  • Stage IV disease

    • Any T
    • Any N
    • M1 (distant metastases present)
    • Recurrent lung cancer in a separate lobe after resection or radiotherapy within the past 5 years OR multifocal lesions in > 1 lobe considered stage IV disease
• New lesions occurring ≥ 5 years after resection may be considered a separate primary cancer and are not allowed if this is the only focus of lung cancer

• Measurable and/or nonmeasurable disease by CT scan, positron emission tomography scan, or MRI

  • Disease must be present outside a previous radiotherapy field OR a new lesion must be inside the port
  • Measurable disease must be assessed within the past 28 days
  • Nonmeasurable disease must be assessed within the past 42 days
  • Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease
• Must be a lifelong nonsmoker (< 100 cigarettes in lifetime)
• Treated brain metastases allowed provided the patient is asymptomatic and do not require steroids

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin normal
• SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
• Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases present)
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
• Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Hypertension allowed if controlled on medication prior to study enrollment
• Must be willing to provide prior smoking history
• No immediate life-threatening complications from malignancies
• No prior major medical condition, psychological condition, or social situation that would preclude study treatment
• No hemoptysis ≥ ½ teaspoon within the past 28 days
• No clinical history of pulmonary or upper respiratory hemorrhage ≥ grade 2 within the past 6 months or grade 1 within the past 28 days
• No history of either thrombosis or hemorrhage, including hemorrhagic or thrombotic stroke, or other CNS bleeding
• No serious nonhealing wound, ulcer, or bone fracture

• No other prior malignancy except for the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • Adequately treated stage I or II cancer from which the patient is currently in complete remission
  • In situ cervical cancer
  • Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 7 days since prior fine-needle aspiration or core biopsy
• At least 28 days since prior radiotherapy (14 days for palliative radiotherapy) and recovered
• At least 28 days since prior surgery (e.g., thoracic or other major surgeries) and recovered
• At least 28 days since prior systemic chemotherapy
• Prior biologic therapy allowed
• No prior gefitinib, erlotinib hydrochloride, bevacizumab, or other targeted therapies against the epidermal growth factor receptor or vascular endothelial growth factor axes
• Concurrent stable, therapeutic anticoagulation therapy allowed (e.g., warfarin or low molecular weight heparin), provided the patient has no history of bleeding complications on anticoagulation or an inability to establish a stable therapeutic regimen for anticoagulation
• No concurrent surgery
• No other concurrent nonprotocol treatment (including chemotherapy, hormonal therapy, biological therapy, or radiotherapy) directed at this cancer